首页 | 本学科首页   官方微博 | 高级检索  
文章检索
  按 检索   检索词:      
出版年份:   被引次数:   他引次数: 提示:输入*表示无穷大
  收费全文   7599篇
  免费   647篇
  国内免费   3篇
  2024年   6篇
  2023年   52篇
  2022年   137篇
  2021年   234篇
  2020年   147篇
  2019年   159篇
  2018年   189篇
  2017年   153篇
  2016年   295篇
  2015年   480篇
  2014年   520篇
  2013年   614篇
  2012年   757篇
  2011年   642篇
  2010年   450篇
  2009年   387篇
  2008年   457篇
  2007年   458篇
  2006年   399篇
  2005年   331篇
  2004年   303篇
  2003年   318篇
  2002年   239篇
  2001年   43篇
  2000年   35篇
  1999年   49篇
  1998年   49篇
  1997年   36篇
  1996年   33篇
  1995年   22篇
  1994年   16篇
  1993年   24篇
  1992年   38篇
  1991年   13篇
  1990年   13篇
  1989年   10篇
  1988年   10篇
  1987年   14篇
  1986年   9篇
  1985年   6篇
  1984年   7篇
  1983年   11篇
  1982年   7篇
  1981年   5篇
  1980年   10篇
  1979年   5篇
  1978年   8篇
  1976年   4篇
  1975年   11篇
  1937年   3篇
排序方式: 共有8249条查询结果,搜索用时 15 毫秒
991.
Symbionts are widespread and might have a substantial effect on the outcome of interactions between species, such as in host-parasitoid systems. Here, we studied the effects of symbionts on the outcome of host-parasitoid interactions in a four-partner system, consisting of the parasitoid wasp Leptopilina boulardi, its two hosts Drosophila melanogaster and D. simulans, the wasp virus LbFV, and the endosymbiotic bacterium Wolbachia. The virus is known to manipulate the superparasitism behavior of the parasitoid whereas some Wolbachia strains can reproductively manipulate and/or confer pathogen protection to Drosophila hosts. We used two nuclear backgrounds for both Drosophila species, infected with or cured of their respective Wolbachia strains, and offered them to L. boulardi of one nuclear background, either infected or uninfected by the virus. The main defence mechanism against parasitoids, i.e. encapsulation, and other important traits of the interaction were measured. The results showed that virus-infected parasitoids are less frequently encapsulated than uninfected ones. Further experiments showed that this viral effect involved both a direct protective effect against encapsulation and an indirect effect of superparasitism. Additionally, the Wolbachia strain wAu affected the encapsulation ability of its Drosophila host but the direction of this effect was strongly dependent on the presence/absence of LbFV. Our results confirmed the importance of heritable symbionts in the outcome of antagonistic interactions.  相似文献   
992.

Background

Until 2008, human rabies had never been reported in French Guiana. On 28 May 2008, the French National Reference Center for Rabies (Institut Pasteur, Paris) confirmed the rabies diagnosis, based on hemi-nested polymerase chain reaction on skin biopsy and saliva specimens from a Guianan, who had never travelled overseas and died in Cayenne after presenting clinically typical meningoencephalitis.

Methodology/Principal Findings

Molecular typing of the virus identified a Lyssavirus (Rabies virus species), closely related to those circulating in hematophagous bats (mainly Desmodus rotundus) in Latin America. A multidisciplinary Crisis Unit was activated. Its objectives were to implement an epidemiological investigation and a veterinary survey, to provide control measures and establish a communications program. The origin of the contamination was not formally established, but was probably linked to a bat bite based on the virus type isolated. After confirming exposure of 90 persons, they were vaccinated against rabies: 42 from the case''s entourage and 48 healthcare workers. To handle that emergence and the local population''s increased demand to be vaccinated, a specific communications program was established using several media: television, newspaper, radio.

Conclusion/Significance

This episode, occurring in the context of a Department far from continental France, strongly affected the local population, healthcare workers and authorities, and the management team faced intense pressure. This observation confirms that the risk of contracting rabies in French Guiana is real, with consequences for population educational program, control measures, medical diagnosis and post-exposure prophylaxis.  相似文献   
993.
Hormone therapy and anti-ErbB2 therapies are prescribed according to the hormone receptor [estrogen receptor α (ERα)/progesterone receptor] and ErbB2 status of the initial tumor, but it appears that circulating tumor cells (CTCs) and, consequently, the metastatic cells may have a different receptor status. As an attempt to meet the crucial need for identification of the subpopulation of patients that will benefit from more individualized therapies, rapidly evolving therapies should allow a profiling of the tumors and/or of the CTCs. We established a triple fluorescence staining using eight cell lines to visualize the CTCs (cytokeratin detection) and then to define their individual ERα and ErbB2 status. Afterward, we used this method for blood samples from 26 metastatic breast cancer patients. We identified major differences of ERα levels between the cell lines and even within one cell line. For the metastatic patients, we detected and characterized CTCs in 38.5% of the patients with a total of 92 CTCs. We could demonstrate that at least 69.6% of the CTCs exhibit an ERα and/or ErbB2 status different from the status of the primary tumor and that the CTCs from only 30% of the patients had no change of receptor status. Strikingly, heterogeneities of the status, aggregation, and size clearly appear within the CTCs. The data we generated outline the importance of a profiling not only of tumors but also of CTCs to establish individualized treatments. CTCs may then appear as new prognosis and treatment marker for both metastatic and adjuvant breast cancers.  相似文献   
994.
This paper presents an operations planning scheme based on mathematical programming models (specifically, Mixed-Integer Linear Programming (MILP) models) integrated into a web-enabled Advanced Planning and Scheduling System (APS), developed for and implemented in an engine assembler that supplies the car industry. One objective of this paper is to provide empirical insights into some operations planning characteristics in the automotive industry. The other main objective is to show MILP models and their use to create plans that enable the coordination of different planning levels (mid-term and short-term) and planning domains (procurement, production and distribution). The APS fulfills the requirements of an engine assembler in the automotive sector (namely lean-type constraints and objectives). The system is based on two MILP models, which have been purposely developed together along with their relations. The models presented herein provide a solution that considers supply chain objectives and constraints, and are integrated by means of data and constraints which have proven sufficient to fulfill users?? and stakeholders?? requirements. This case study presents the models?? most relevant aspects and their implementation.  相似文献   
995.
One puzzling observation in patients affected with Hutchinson-Gilford progeria syndrome (HGPS), who overall exhibit systemic and dramatic premature aging, is the absence of any conspicuous cognitive impairment. Recent studies based on induced pluripotent stem cells derived from HGPS patient cells have revealed a lack of expression in neural derivatives of lamin A, a major isoform of LMNA that is initially produced as a precursor called prelamin A. In HGPS, defective maturation of a mutated prelamin A induces the accumulation of toxic progerin in patient cells. Here, we show that a microRNA, miR-9, negatively controls lamin A and progerin expression in neural cells. This may bear major functional correlates, as alleviation of nuclear blebbing is observed in nonneural cells after miR-9 overexpression. Our results support the hypothesis, recently proposed from analyses in mice, that protection of neural cells from progerin accumulation in HGPS is due to the physiologically restricted expression of miR-9 to that cell lineage.  相似文献   
996.
Landscape fragmentation usually has a considerable effect on the genetic and demographic viability of most species because it reduces population size and increases isolation among populations. This situation provokes loss of genetic diversity and increased inbreeding that can lead to population or species extinctions. Some studies also show that landscape fragmentation may have no effect on or even positive consequences for species genetic diversity. The protected tarantula, Brachypelma vagans, exhibits a particular situation in the Mexican Caribbean, which has experienced high lowland and coastal fragmentation because of recent increases in agricultural, urban and touristic development. This modified landscape structure creates favorable conditions for establishment of B. vagans populations in rural settlements. Populations of this tarantula have high densities of individuals, principally females and juveniles, and gene dispersion is assumed by the rare males. Within this context, we studied the influence of natural and anthropogenic fragmentation on the genetic diversity of six B. vagans populations (five continental, one insular), together with their spatial organization. Our approach used seven inter simple sequence repeat markers, which are highly polymorphic markers. The 76 loci selected revealed high genetic variability for continental populations and a low, but not critical situation, for the insular population. We detected a good level of gene exchange among continental populations, and an evident and recent isolation of the island population. This species exhibits a metapopulation structure in the lowlands with numerous local populations where mature females exhibit high birth site fidelity. We conclude that this protected species does not exhibit characteristics to warrant its current conservation status, and we propose complete revision of the ecological and genetic situation for B. vagans in particular, and for all species within the genus Brachypelma in general.  相似文献   
997.
998.
999.
The superfamily Testudinoidea is the most diverse and widely distributed clade of extant turtles. Surprisingly, despite an extensive fossil record, and increasing amount of molecular data available, the temporal origin of this group is still largely unknown. To address this issue, we used a comprehensive molecular dataset to perform phylogenetic and molecular dating analyses, as well as seven fossil constraints to calibrate the ages of the nodes in the phylogeny. The molecular dataset includes the complete mitochondrial genomes of 37 turtle species, including newly sequenced mitochondrial genomes of Phrynops hilarii, Emys orbicularis, Rhinoclemmys punctularia, and Chelonoidis nigra, and four nuclear markers. Our results revealed that the earliest divergences within crown testudinoids occurred around 95.0 Mya, in the early Late Cretaceous, earlier than previously reported, raising new questions about the historical biogeography of this group.  相似文献   
1000.
TM9 proteins form a family of conserved proteins with nine transmembrane domains essential for cellular adhesion in many biological systems, but their exact role in this process remains unknown. In this study, we found that genetic inactivation of the TM9 protein Phg1A dramatically decreases the surface levels of the SibA adhesion molecule in Dictyostelium amoebae. This is due to a decrease in sibA mRNA levels, in SibA protein stability, and in SibA targeting to the cell surface. A similar phenotype was observed in cells devoid of SadA, a protein that does not belong to the TM9 family but also exhibits nine transmembrane domains and is essential for cellular adhesion. A contact site A (csA)-SibA chimeric protein comprising only the transmembrane and cytosolic domains of SibA and the extracellular domain of the Dictyostelium surface protein csA also showed reduced stability and relocalization to endocytic compartments in phg1A knockout cells. These results indicate that TM9 proteins participate in cell adhesion by controlling the levels of adhesion proteins present at the cell surface.  相似文献   
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号